Etoxadrol‐meta‐isothiocyanate: A potent, enantioselective, electrophilic affinity ligand for the phencyclidine‐binding site

FEBS Letters

Rice, Kenner C.¹  Mattson, Mariena V.¹  Huguenin, Philip N.¹  Jacobson, Arthur E.¹  Thurkauf, Andrew¹ 

[1] Section on Drug Design and Synthesis, Laboratory of Neuroscience, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Phencyclidine-binding site;    Etoxadrol-meta-isothiocyanate;    Etoxadrol;    1;    3-Dioxolane;    Electrophilic affinity ligand;    Enantioselective irreversible ligand;    etoxadrol-meta-isothiocyanate;    2S;    4S;    6S-2-ethyl-2-(3-isothiocyanatophenyl)-2-piperidyl)-1;    3-dioxolane;    metaphit;    1-[1-(3-isothiocyanatophenyl)cyclohexyl]piperidine;    PCP;    phencyclidine;   

DOI  :  10.1016/0014-5793(88)80514-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Etoxadrol-meta-isothiocyanate (2S,4S,6S-2-ethyl-2-(3-isothiocyanatophenyl)-2-piperidyl)1,3-dioxolane, 4a) has been synthesized and characterized as an irreversible ligand for the phencyclidine (PCP)-binding site. It is the first chiral electrophilic affinity ligand for this site to have been described. This affinity ligand is based upon etoxadrol, a 1,3-dioxolane known to have PCP-like effects in vivo and in vitro. Etoxadrol-meta-isothiocyanate was found to be four–five times more potent in vitro than metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]piperidine), the only previously known electrophilic affinity ligand for the PCP-binding site. The binding was shown to be highly enantioselective for etoxadrol-meta-isothiocyanate (4a). The 2R,4R,6R-enantiomer of 4a was essentially inactive. The ability of the 2S,4S,6S-enantiomer (4a) to interact with the benzodiazepine, muscarinic, and mu opioid receptor systems was also examined, and it was found not to interact with these receptor systems. It seems likely that 4a will prove to be a valuable tool in the study of structure and function of the PCP-binding site.

【 授权许可】

Unknown